Beta Blockers

Beta blockers, also known as beta-adrenergic blocking agents, are a class of drugs that works by blocking the neurotransmitters norepinephrine and epinephrine from binding to receptors. There are three known types of beta receptors, known as beta₁ (β₁), beta₂ (β₂) and beta₃ (β₃).

• β₁-adrenergic receptors are located commonly in the heart and kidneys.
  
  
• β₂-adrenergic receptors are located mainly in the lungs, gastrointestinal tract, liver, uterus, vascular smooth muscle, and skeletal muscle.
  
  
• β₃- adrenergic receptors are located in fat cells.

When the neurotransmitters are prevented from binding to the receptors, it in turn causes the effects of adrenaline (epinephrine) to be blocked. This action allows the heart to relax and beat more slowly thereby reducing the amount of blood that the heart must pump. Over time, this action improves the pumping mechanism of the heart.

Beta blockers are used to manage a variety of conditions. They include, but are not limited to:

• cardiac arrhythmias,
  
  
• heart failure,
  
  
• high coronary artery disease risk,
  
  
• diabetes,
  
  
• post heart attack (myocardial infarction),
  
  
• angina pectoris due to coronary atherosclerosis, and
  
  
• hypertension (high blood pressure). (In the management of hypertension, it may be used alone or concomitantly with other antihypertensive agents, particularly thiazide diuretics).

Off-label uses of beta blockers include, but are not limited to:

• migraine headaches,
  
  
• glaucoma,
  
  
• hyperthyroidism,
  
  
• fibromyalgia,
  
  
• generalized anxiety disorder,
  
  
• parkinsonian tremor, and
  
  
• atrial fibrillation.

Beta blockers differ by which receptors are blocked.

First generation beta blockers such as propranolol (Inderal, InnoPran), nadolol (Corgard), timolol maleate  (Blocadren), penbutolol sulfate (Levatol), sotalol hydrochloride (Betapace), and pindolol (Visken) are non-selective in nature, meaning that they block both beta₁ (β₁) and beta₂ (β₂) receptors and will subsequently affect the heart, kidneys, lungs, gastrointestinal tract, liver, uterus, vascular smooth muscle, and skeletal muscle and as an effect, could cause reduced cardiac output, reduced renal output amongst other actions.

Second generation beta blockers such as metoprolol (Lopressor, Toprol XL), acebutolol hydrochloride (Sectral), bisoprolol fumarate (Zebeta), esmolol hydrochloride (Brevibloc), betaxolol hydrochloride (Kerlone), and acebutolol hydrochloride (Sectral) are selective, as they block only β₁ receptors and as such will affect mostly the heart and cause reduced cardiac output.

Beta blockers such as pindolol (Visken), penbutolol sulfate (Levatol), and acebutolol hydrochloride (Sectral) differ from other beta blockers as they possess intrinsic sympathomimetic activity (ISA), which means they mimic the effects of epinephrine and norepinephrine and can cause an increase in blood pressure and heart rate. ISA's have smaller effects in reducing resting cardiac output and resting heart rate, in comparison to drugs that do not possess ISA.

Beta blocker such as propranolol (Inderal, InnoPran), acebutolol hydrochloride (Sectral), and betaxolol hydrochloride (Kerlone) possess a quinidine-like or anesthetic-like membrane action, which affects cardiac action potential (electrical impulses within the heart that cause contractions).

Beta blockers such as labetalol hydrochloride (Trandate, Normodyne) and carvedilol (Coreg)
 have both β- and α₁-adrenergic receptors. Blocking the α₁-adrenergic receptors in addition to the β blocker lowers blood pressure which provides additional vasodilatory action of the arteries.

Beta blockers are usually well tolerated and most adverse events are mild. Beta blockers may cause diarrhea, stomach cramps, nausea and vomiting. Rash, blurred vision, muscle cramps, and fatigue have also been reported. Beta blockers may cause hypoglycemia or hyperglycemia and mask the symptoms of hypoglycemia in diabetic patients. Effects on the heart and circulatory system include bradycardia (slow heart rate), hypotension (low blood pressure), heart failure or heart block in patients with heart problems, cold extremities due to reduced circulation. Abrupt withdrawal of beta blockers may worsen angina (chest pain) and cause heart attacks or sudden death. Effects on the central nervous system include headache, depression, confusion, dizziness, nightmares, and hallucinations. Beta blockers may cause shortness of breath in asthmatics. Sexual dysfunction may also occur.

Beta blockers [pindolol (Visken) and propranolol (Inderal, InnoPran)] should not be taken with phenothiazines [thioridazine and chlorpromazine (Thorazine)] as this will cause an increase in blood plasma levels of either or both classes of drugs. Due to the fact that increased levels of thioridazine could increase the risk of life-threatening cardiac arrhythmias, thioridazine is contraindicated in patients receiving pindolol and propranolol.

Beta blockers [acebutolol hydrochloride (Sectral), atenolol (Tenormin), betaxolol hydrochloride (Kerlone), carteolol hydrochloride (Cartrol), esmolol hydrochloride (Brevibloc), metoprolol (Lopressor, Toprol XL), nadolol (Corgard), penbutolol sulfate (Levatol), pindolol (Visken), propranolol (Inderal, InnoPran), and timolol maleate (Blocadren)] when taken with verapamil (Calan, Verelan, Verelan PM, Isoptin, Isoptin SR, Covera-HS), will cause an increase of blood plasma levels of either drug. It is important to monitor cardiac function due to additive effects of both drugs.

Beta blockers [acebutolol hydrochloride (Sectral), atenolol (Tenormin), betaxolol hydrochloride (Kerlone), carteolol hydrochloride (Cartrol), esmolol hydrochloride (Brevibloc), metoprolol (Lopressor, Toprol XL), nadolol (Corgard), penbutolol sulfate (Levatol), pindolol (Visken), propranolol (Inderal, InnoPran), and timolol maleate (Blocadren)], when taken with clonidine (Catapres), could cause life-threatening increases in blood pressure. It is important to monitor blood pressure continuously.

Beta blockers [carteolol hydrochloride (Cartrol), nadolol (Corgard), penbutolol sulfate (Levatol), pindolol (Visken), propranolol (Inderal, InnoPran), and timolol maleate (Blocadren), sotalol hydrochloride (Betapace)] when taken with beta-agonists (albuterol, arformoterol, bitolterol, formoterol (Foradil, Foradil Certihaler, Perforomist), levalbuterol (Xopenex) and salmeterol (Serevent Discus)] could affect the pulmonary organs and may cause bronchospasm.

Beta blockers [metoprolol (Lopressor, Toprol XL) and propranolol (Inderal, InnoPran)] when taken with barbiturates [phenobarbital, primidone (Mysoline), amobarbital, butabarbital (Butisol), mephobarbital (Mebaral), and secobarbital], cause a reduction of blood plasma levels of the mentioned beta blockers. Higher doses of beta blockers are sometimes given if an interaction is suspected.

Beta-Adrenergic Blocking Agents

• acebutolol hydrochloride (Sectral)
  
  
• atenolol (Tenormin)
  
  
• betaxolol hydrochloride (Kerlone)
  
  
• bisoprolol fumarate (Zebeta)
  
  
• carteolol hydrochloride (Cartrol)
  
  
• esmolol hydrochloride (Brevibloc)
  
  
• metoprolol (Lopressor, Toprol XL)
  
  
• penbutolol sulfate (Levatol)
  
  
• nadolol (Corgard)
  
  
• nebivolol (Bystolic)
  
  
• pindolol (Visken)
  
  
• propranolol (Inderal, InnoPran)
  
  
• timolol maleate (Blocadren)
  
  
• sotalol hydrochloride (Betapace)

Alpha/Beta-Adrenergic Blocking Agents

• carvedilol (Coreg)
  
  
• labetalol hydrochloride (Trandate, Normodyne)